PXD025105

PXD025105 is an original dataset announced via ProteomeXchange.

Title	Mapping the Interaction between Eukaryotic Initiation Factor 4A (eIF4A) and the Inhibitor Hippuristanol Using Carbene Footprinting and Mass Spectrometry
Description	Protein-ligand interactions are central to protein activity and cell functionality. Improved knowledge of these relationships greatly benefits our understanding of key biological processes and aids in rational drug design towards the treatment of clinically relevant diseases. Carbene footprinting is a recently developed mass spectrometry-based chemical labelling technique that provides valuable information relating to protein-ligand interactions, such as the mapping of binding sites and associated conformational change. Here we show the application of carbene footprinting to the interaction between eIF4A helicase and a natural product inhibitor, hippuristanol, found in the coral Isis hippuris. Upon addition of hippuristanol we identified reduced carbene labelling (masking) in regions of eIF4A previously implicated in ligand binding. Additionally, we detected hippuristanol-associated increased carbene labelling (unmasking) around the flexible hinge region of eIF4A, indicating ligand-induced conformational change. This work represents further development of the carbene footprinting technique and demonstrates its potential in characterising medicinally relevant protein-ligand interactions.
HostingRepository	PRIDE
AnnounceDate	2021-08-25
AnnouncementXML	Submission_2021-08-25_04:45:23.668.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	James Lloyd
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ FT

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-30 10:40:53	ID requested
1	2021-08-25 04:07:40	announced
⏵ 2	2021-08-25 04:45:24	announced	2021-08-25: Updated project metadata.

10.1002/PMIC.202000288;

Lloyd JR, Hogan A, Paschalis V, Bellamy-Carter J, Bottley A, Seymour GB, Hayes CJ, Oldham NJ, Mapping the interaction between eukaryotic initiation factor 4A (eIF4A) and the inhibitor hippuristanol using carbene footprinting and mass spectrometry. Proteomics, 21(21-22):e2000288(2021) [pubmed]

submitter keyword: protein footprinting, mapping ligand binding,Carbene labelling

Neil J. Oldham
contact affiliation	University of Nottingham, Nottingham, United Kingdom
contact email	pcznjo@nottingham.ac.uk
lab head
James Lloyd
contact affiliation	University of Nottingham
contact email	james.lloyd@nottingham.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/08/PXD025105

PRIDE project URI

• PRIDE
  1. PXD025105
     1. Label: PRIDE project
     2. Name: Mapping the Interaction between Eukaryotic Initiation Factor 4A (eIF4A) and the Inhibitor Hippuristanol Using Carbene Footprinting and Mass Spectrometry